Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma

Stojšić, Jelena; Stanković, Tijana; Stojković, Sonja; Milinkovic, Vedrana; Dinić, Jelena; Milošević, Zorica; Milovanović, Zorka; Tanić, Nikola; Banković, Jasna

doi:10.1016/j.yexmp.2014.11.010

Cited by 3 publications

(2 citation statements)

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“…We observed a clear trend suggesting that only patients with tumors exhibiting high nuclear pAKT or low pERK expression may benefit from this treatment, while this therapy may not be a good option for tumors with the opposite characteristics. In line with these results, high pAKT levels have been linked to better response to neoadjuvant chemotherapy in breast cancer patients [ 54 ], and low pERK expression has been correlated with longer survival of NSCLC patients receiving neoadjuvant chemotherapy [ 55 ]. However, other retrospective studies have shown contrasting results, suggesting that high-pERK- and low-pAKT-expressing NSCLC tumors are the tumors that respond to adjuvant chemotherapy [ 28 ].…”

Section: Discussionmentioning

confidence: 92%

Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer

et al. 2018

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Lung tumors represent a major health problem. In early stage NSCLC tumors, surgical resection is the preferred treatment, but 30-55% of patients will relapse within 5 years after surgery. Thus, the identification of prognostic biomarkers in early stage NSCLC patients, especially those which are therapeutically addressable, is crucial to enhance survival of these patients. We determined the immunohistochemistry expression of key proteins involved in tumorigenesis and oncogenic signaling, p53, EGFR, pAKT and pERK, and correlated their expression level to clinicopathological characteristics and patient outcome. We found EGFR expression is higher in the squamous cell carcinomas than in adenocarcinomas (p=0.043), and that nuclear p53 staining correlated with lower differentiated squamous tumors (p=0.034). Regarding the prognostic potential of the expression of these proteins, high pERK levels proved to be an independent prognostic factor for overall (p<0.001) and progression-free survival (p<0.001) in adenocarcinoma patients, but not in those from the squamous histology, and high p53 nuclear levels were identified as independent prognostic factor for progression-free survival (p=0.031) only in squamous cell carcinoma patients. We propose a role as early prognostic biomarkers for pERK protein levels in adenocarcinoma, and for nuclear p53 levels in squamous cell lung carcinoma. The determination of these potential biomarkers in the adequate histologic context may predict the outcome of early stage NSCLC patients, and may offer a therapeutic opportunity to enhance survival of these patients.

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Section: Discussionmentioning

confidence: 92%

Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer

et al. 2018

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“…However, NSCLC cells developed resistance to chemotherapy. That is one of the main reasons that the patients get poor outcomes (5-year over survival < 10%) [13–15]. Furthermore, neoadjuvant chemotherapy was usually in experimental phases, and only a few patients get ideal effects [5].…”

Section: Discussionmentioning

confidence: 99%

Ku80 correlates with neoadjuvant chemotherapy resistance in human lung adenocarcinoma, but reduces cisplatin/pemetrexed-induced apoptosis in A549 cells

et al. 2017

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BackgroundKu80 is a DNA repair protein which involves in cell apoptosis and chemoresistance. However, it is unclear whether Ku80 correlates with the efficiency of neoadjuvant chemotherapy in human lung adenocarcinoma, and modulates cisplatin/pemetrexed-induced lung cancer cell apoptosis in vitro.MethodsWe recruited 110 patients with stage IIIA lung adenocarcinoma, who received 2 cycles of neoadjuvant chemotherapy, and their lungs were reevaluated by CT scan. Immunohistochemistry and qRT-PCR was performed to detect the expression level of Ku80. A549 cells were transfected by lentiviral vector containing shRNA and full length cDNA to knockdown or upregulate Ku80 gene expression. CCK8 assay, flow cytometry and Western blot were employed to determine the viability and apoptosis of A549 cells treated with cisplatin combined with pemetrexed.ResultsKu80 expression was detected in 76 patients (69%). There were 38 patients who responded to chemotherapy, where Ku80 was positively expressed in 7 cases (18.4%). Immunohistochemical score of Ku80 protein in the response group (2.079 ± 1.617) to chemotherapy was lower than that in the nonresponse group (5.597 ± 2.114, P < 0.05). Tissue samples from the nonresponse group exhibited higher Ku80 mRNA levels compared to the response group. Ku80 knockdown by shRNA augmented cisplatin/pemetrexed-induced decline in viability, whereas Ku80 overexpression attenuated viability reduction induced by these drugs compared to control A549 cells. Both flow cytometry and Western blot analysis displayed that the apoptotic rate of Ku80 shRNA-transfected A549 cells was significantly increased compared to control cells treated with cisplatin/pemetrexed, which was lowered by Ku80 overexpression.ConclusionKu80 could predict the probability of resistance to neoadjuvant chemotherapy in lung adenocarcinoma, and reduced cisplatin and pemetrexed-induced apoptosis in A549 cells.

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Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells

Kucińska

Piotrowska‐Kempisty

Lisiak

et al. 2016

Toxicology in Vitro

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Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma

Cited by 3 publications

References 27 publications

Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer

Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer

Ku80 correlates with neoadjuvant chemotherapy resistance in human lung adenocarcinoma, but reduces cisplatin/pemetrexed-induced apoptosis in A549 cells

Selective anticancer activity of the novel thiobenzanilide 63T against human lung adenocarcinoma cells

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